Title:Design and Facile Synthesis of Spiro-s-tetrazine Derivatives of 2,4-
diphenyl-3-azabicyclo[3.3.1]nonane-9-one
Volume: 20
Issue: 3
Author(s): Manini Nayak, Kanyanjali Samal and Anita Pati*
Affiliation:
- Department of Chemistry, School of Applied Sciences, KIIT Deemed to be University, Bhubaneswar-751024, Odisha, India
Keywords:
Diphenyl-3-azabicyclo[3.3.1]nonan-9-one, spiroheterocycles, tetrazines, thiazolidinone, mannich reaction, azabicyclic ketone.
Abstract:
Background: Literature survey suggested various methods of synthesis of the 3-
azabicyclo [3.3.1] nonanes which include, Mannich reaction, α, α'-Annelation of Cyclic Ketones or
through Enamines, Michael addition, Intramolecular Cyclizations, etc. However, a mechanism following
a Michael addition path through the formation of the dibenzylidene cyclohexanone intermediate
can not be ignored. Thus to ensure the mechanistic pathway for the formation of 2,4-diphenyl-
3-azabicyclo[3.3.1]nonan-9-one and to understand the reactivity of a conformationally and biologically
important molecule for the synthesis of spiro-s-tetrazine derivatives and its further functionalization
with thiazole and thiazolidinone derivatives the present work has been undertaken.
Methods: Direct reaction of dibenzylidene cyclohexanone and ammonium acetate has been tried to
get the confirmation of Mannich/ Michael reaction pathway for the formation of 2,4-diphenyl-3-
azabicyclo[3.3.1]nonan-9-one. Synthesis of the spiro-s-tetrazine derivative has been accomplished
by the simple condensation reaction of azabicyclic system and thiocarbohydrazide (TCH). Simple
methods have been adopted for the installation of heterocyclic moieties like thiazolidinone, thiazole.
Results: Failure of the attempts to prepare 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-onedirectly
from dibenzylidene cyclohexanone ruins the possibility of Michael addition reaction and supports
the formation of the product through Mannich reaction. Synthesis of the spiro derivatives containing
tetrazine, thiazole, thiazolidinone moieties were achieved by using simple techniques and products
were obtained in good yield. FTIR, NMR spectroscopy are used for the characterization of all
the molecules. Formation of 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-onewas confirmed by using
some additional data like mass and single crystal XRD.
Conclusion: Confirmation of the mechanistic route for the 2 2,4-diphenyl-3-
azabicyclo[3.3.1]nonan-9-one was achieved and simple methods for the formation of spiro derivatives
containing tetrazine, thiazole, thiazolidinone were established.
